Medicinal compositions



ite dttes atent O F 3,117,910 NEDICINAL CGMPGSITIGNS Eacoh fisterweil, 1001 .icrorne Ave., Bronx 52, N.Y. No Drawing. Filed Nov. 15, 1961, Ser. No. 152,618 9 Claims. (Cl. 167-65) This invention is a novel composition of matter having antispasmodic, sedative and hypnotic action.

There are known proprietary sedative and hypnotic compositions which contain a sedative agent or an antihistamine agent, generally in combination with an antispasmodic compound such as scopolamine or like alkaloid. The antispasrnodic is for the purpose of controlling the muscular and nervous tension which often accompanies insomnia and other conditions in which a sed-gtive medicine is indicated. Such compositions containin scopolamine are potentially dangerous in causing untoward side reactions or toxic manifestations, of which dizziness, disturbed co-ordination, dryness of the mouth, palpitation, and blurring of the vision may be cited as illustrative, and such compositions carry strict warnings to discontinue their use in the event symptoms of the above nature are observed.

it is an object of this invention to provide an effective antispasmodic which is safe and may be used alone or in combination with sedative and analgesics.

It is a further object of the present invention to provide a novel medicinal composition which is effective as a sedative and hypnotic and which is so safe in its action that no caution label is needed.

Ari additional object of this invention is to provide a potentiated composition wherein the desired therapeutic activity is obtained with minimal dosage.

It has now been found that Euphorbia pilulifera, an antispasmodic of long standing may be used in combination vith para aminobenzoic acid to provide a safe, effective anti spasmodic in dosages one-tenth of normal. The U5. Dispensatory, 25th edition, 1955, describes Euphorbia as having an active principle which is irritating to the stomach in large doses. The former ofiicial dose, National Formulary VII, was stated to be ab at 30 grains of the dried drug. It is commercially available as powdered extracts wherein one part represents four or five parts of the dried drug. Pillular and fluid extracts are also available. As a result of its tendency to produce gastritis Euphorbia has fallen into more or less disuse but the present i vention makes it possible to obtain the desired antispasmodic action of Euphorbia without the likelihood of producing stomach irritation. By using para aminobenzoic acid in approximately 100% to 200% by weight of the Euphorbia, the dose of the Euphorbia may be reduced to its normal value without loss of etficacy. For example a combination of grain of the powdered extract or" Euphorbia (4:1) with 1 grain of para aminobenzoic acid exhibits the approximate etiect of 7.5 grains of the powdered extract without gastric irritation.

There is thus provided a safe, eiiicacious antispasmodic which may advantageously be combined with other ingredients such as sedatives, analgesics and antihistamines. Sedative compounds include the barbiturates, codeine, morphine, chloral hydrate, bromisovalum, acetylcarbromal, bromides such as ammonium bromide, and various vegetable drugs such as Passiflom incarnata, etc. Analgesics include those of the benzene series such as salicylarnide, aspirin, acetanilide, phenacetin; the salicylates such as sodium salicylate; phenyl cinchonic acid; and similar compounds having like physiological activity. Antihistamine compounds include pyrilamine m-aleatejmethapyrilene hydrochloride,* chlor-pheniramine maleate See Merck Index, 6th ed.

Ejl'lfilfi Patented Jan. 14, 1954 "ice (U.S.P.),clemizole hydrochloride (1 p chlorobenzyl-2- pyrrolidyl-methyl benzirnidazole HCl), thonzylamine hydrochloridej tripelennamine citratef meclizine hydrochloride (New and Nonoiiicial Drugs 1960), and cyclizine hydrochloride, etc. A particularly effective and advantageous medication for sedation and hypnotic action results from the combination of the four ingredients; powdered extract of Euphorbia, powdered extract of Passiflora, salicylamide and para aminobenzoic acid. The inclusion of the para aminobenzoic acid in such a combination potentiates the sedative and hypnotic action of the other components to an extent not expected from a knowledge of their properties. Examples illustrative of the practice of this invention are given below wherein one part of the extracts represents four parts of the dried drug.

Example 1 Extra Grains Powdered extract of Euphorbia pilulifei-a 0.75

Para aminobenzoic acid 1.00

Example 2 Powdered extract of Euphorbia 1 Para aminobenzoic acid 1 Example 3 Powdered extract of Euphorbia l Para aminobenzoic acid 2 Example 4 Powdered extract Euphorbia 0.75

Codeine sulfate 0.25

Para aminobenzoic acid 1.00

Example 5 Powdered extract Euphorbia .75

Phenobarbital .25

Para aminobenzoic acid 1.00

Example 6 Powdered extract Euphorbia .75

Powdered extract Passz'flora incarnata .75

Para aminobenzoic acid 1.00

Example 7 Powdered extract Euphorbia 0.75

Aspirin 3.00

Para aminobenzoic acid 1.00

Example 8 Powdered extract Euphorbia 0.75

Salicylamide 3.00

Para aminobenzoic acid 1.00

Example 9 Powdered extract Euphorbia 0.75

Salicylamide 3.00

Powdered extract Passifiora 0.75

Para aminobenzoic acid 1.00

Example 10 Powdered extract Euphorbia 0.75

Salicylamide 3.00

Methapyrilene hydrochloride 0.38

Para aminobenzoic acid 1.00

Example 11 Powdered extract Euphorbia 0.75

Salicylamide 3.00

Powdered extract Passiflora 0.75

Methapyrilene hydrochloride 0.38

Para aminobenzoic acid 1.00

Compositions may be prepared where the vegetable drugs are used in their equivalent forms such as the fluid extract or tincture, when such would be more desirable than the powdered extract. The compositions may also be made in various dosage forms such as tablets, capsules, or liquids utiiizing the usual pharmaceutical carriers known to the at. They may be safely used for insomnia, nervous tension, asthma, and in other conditions Where antispasmcdic, sedative and hypnotic action is desirable.

What is claimed is:

1. A therapeutic composition comprising an extract of Enphorbia pilulifera and para aminohenzoic acid in therapeutically active quantities in a pharmaceutiacl carrier whereby the dose of the Euphorbia is reduced to onetenth of its dose when used without the para aminobenzoic cid.

2. A therapeutic composition comprising an extract of Euphorbza pilulifera and para aminobenzoic acid in therapeutically active quantities where the latter is present in the range of 190% to 209% by weight of the former in a pharmaceutical carrier.

3. A therapeutic composition comprising a sedative, an extract of Ezzphorbia pz'lulifem and para aminobenzoic acid in therapeutically active quantities in a. pharmaceutical carrier whereby. the dose of the Euphorbia is reduced to one-tenth of its dose when used without the para aminobenzoic acid.

4. A therapeutic composition comprising an extract of -Passiflora-incarnata, an extract of Euphorbia pilulifem and para aminobenzoic acid in therapeutically active quantities in a pharmaceutical carrier whereby the dose of the Euphorbia is reduced to one-tenth of its dose when used Without the para aminobenzoic acid.

5. A therapeutic composition comprising an extract of Passiflora incarnata, an extract of Euphorbz'a pilulifera s and para aminobenzoic acid in therapeutically active quantities where the latter is present to the extent of 100% to 200% by weight of the Euphorbia in a pharmaceutical carrier.

6. A therapeutic composition comprising a sedative, an analgesic of the benzene series, an extract of Euplwrbia pilulifem and para aminobcnzoic acid in therapeutically active quantities in a pharmaceutical carrier whereby the dose of the Euphorbia is reduced to one-tenth or" its close when used without the para aminobenzoic acid.

7. A therapeutic composition comprising a sedative, salicylamide, an extract of Euphorbia pilulifera and para aminobenzoic acid in therapeutically active quantities in a pharmaceutical carrier whereby the dose of the Euphorbia is reduced to one-tenth of its dose when used without the para aminobenzoic acid.

8. A therapeutic composition comprising an extract of Passiflora incarnata, salicylamide, an extract of Euphorbia piizzlifera and para aminobenzoic acid in therapeutically active quantities in a pharmaceutical carrier whereby the dose of the Euphorbia is reduced to one-tenth of its dose when used without the para aminobenzoic acid.

9. A therapeutic composition for insomnia comprising the following ingredients in the ratio: powdered extract Passiflom incarnata grain; salicylamide 3 grains; powdered extract Euplzorbia pilulifera /4 grain; and para amniobenzoic acid 1 grain in a pharmaceutical carrier.

References Cited in the file of this patent Burger: Medicinal Chemistry, 1960, Interscience Publ., N.Y., page 231.

Helierman et al.: J. Am. Pharm. Assoc, vol. 39, 1950, pages 142446.

Wilson: American Drug Index, 1960, Lippincott Co., pages 575-576.

Patent No. 3,11%910 January 14 1964 Jacob Osterweil ears in the above numbered pate'r'tified that error app Patent should read as It is hereby o t the said Letters ent requiring correction and the corrected below.

Column 2, line 18, strike out "Extra",

Signed and sealed this 16th day of June 1964 (SEAL) Attest:

EDWARD J. BRENNER ERNEST W. SWIDER Attesting Officer Commissioner of Patents 

1. A THERAPEUTIC COMPOSITION COMPRISING AN EXTRACT OF EUPHORBIA PILULIFERA AND PARA AMINOBENZOIC ACID IN THERAPEUTICALLY ACTIVE QUANTITIES IN A PHARMACEUTICAL CARRIER WHEREBY THE DOSE OF THE EUPHORBIA IS REDUCED TO ONETENTH OF ITS DOSE WHEN USED WITHOUT THE PARA AMINOBENZOIC ACID. 